Activating hidden signals by mimicking cryptic sites in a synthetic extracellular matrix.
Nat Commun
; 14(1): 3635, 2023 06 19.
Article
em En
| MEDLINE
| ID: mdl-37336876
ABSTRACT
Cryptic sites are short signaling peptides buried within the native extracellular matrix (ECM). Enzymatic cleavage of an ECM protein reveals these hidden peptide sequences, which interact with surface receptors to control cell behavior. Materials that mimic this dynamic interplay between cells and their surroundings via cryptic sites could enable application of this endogenous signaling phenomenon in synthetic ECM hydrogels. We demonstrate that depsipeptides ("switch peptides") can undergo enzyme-triggered changes in their primary sequence, with proof-of-principle studies showing how trypsin-triggered primary sequence rearrangement forms the bioadhesive pentapeptide YIGSR. We then engineered cryptic site-mimetic synthetic ECM hydrogels that experienced a cell-initiated gain of bioactivity. Responding to the endothelial cell surface enzyme aminopeptidase N, the inert matrix transformed into an adhesive synthetic ECM capable of supporting endothelial cell growth. This modular system enables dynamic reciprocity in synthetic ECMs, reproducing the natural symbiosis between cells and their matrix through inclusion of tunable hidden signals.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Matriz Extracelular
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article